ARHG2_HUMAN
ID ARHG2_HUMAN Reviewed; 986 AA.
AC Q92974; D3DVA6; O75142; Q15079; Q5VY92; Q8TDA3; Q8WUG4; Q9H023;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 4.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Rho guanine nucleotide exchange factor 2;
DE AltName: Full=Guanine nucleotide exchange factor H1;
DE Short=GEF-H1;
DE AltName: Full=Microtubule-regulated Rho-GEF;
DE AltName: Full=Proliferating cell nucleolar antigen p40;
GN Name=ARHGEF2; Synonyms=KIAA0651, LFP40;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH RHOA AND
RP RAC1, SUBCELLULAR LOCATION, AND DOMAIN COILED-COIL.
RC TISSUE=Cervix carcinoma;
RX PubMed=9857026; DOI=10.1074/jbc.273.52.34954;
RA Ren Y., Li R., Zheng Y., Busch H.;
RT "Cloning and characterization of GEF-H1, a microtubule-associated guanine
RT nucleotide exchange factor for Rac and Rho GTPases.";
RL J. Biol. Chem. 273:34954-34960(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, DOMAIN
RP ZINC-FINGER, AND MUTAGENESIS OF CYS-53 AND TYR-394.
RX PubMed=11912491; DOI=10.1038/ncb773;
RA Krendel M., Zenke F.T., Bokoch G.M.;
RT "Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules
RT and the actin cytoskeleton.";
RL Nat. Cell Biol. 4:294-301(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [4]
RP SEQUENCE REVISION.
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 28-986 (ISOFORMS 1/3).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 630-986 (ISOFORMS 1/2/3).
RX PubMed=2466560;
RA Reddy A.B., Chatterjee A., Rothblum L.I., Black A., Busch H.;
RT "Isolation and characterization of complementary DNA to proliferating cell
RT nucleolar antigen P40.";
RL Cancer Res. 49:1763-1767(1989).
RN [11]
RP PHOSPHORYLATION AT SER-886, AND INTERACTION WITH YWHAZ.
RX PubMed=14970201; DOI=10.1074/jbc.m400084200;
RA Zenke F.T., Krendel M., DerMardirossian C., King C.C., Bohl B.P.,
RA Bokoch G.M.;
RT "p21-activated kinase 1 phosphorylates and regulates 14-3-3 binding to GEF-
RT H1, a microtubule-localized Rho exchange factor.";
RL J. Biol. Chem. 279:18392-18400(2004).
RN [12]
RP PHOSPHORYLATION AT SER-143 AND SER-896, MUTAGENESIS OF SER-143 AND SER-896,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PAK4.
RX PubMed=15827085; DOI=10.1242/jcs.02313;
RA Callow M.G., Zozulya S., Gishizky M.L., Jallal B., Smeal T.;
RT "PAK4 mediates morphological changes through the regulation of GEF-H1.";
RL J. Cell Sci. 118:1861-1872(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-932, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-696, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [15]
RP PHOSPHORYLATION AT SER-886 AND SER-960, INTERACTION WITH AURKA, AND
RP SUBCELLULAR LOCATION.
RX PubMed=17488622; DOI=10.1016/j.devcel.2007.03.014;
RA Birkenfeld J., Nalbant P., Bohl B.P., Pertz O., Hahn K.M., Bokoch G.M.;
RT "GEF-H1 modulates localized RhoA activation during cytokinesis under the
RT control of mitotic kinases.";
RL Dev. Cell 12:699-712(2007).
RN [16]
RP PHOSPHORYLATION AT THR-679, INTERACTION WITH MAPK1, AND MUTAGENESIS OF
RP THR-679.
RX PubMed=18211802; DOI=10.1016/j.bbrc.2008.01.066;
RA Fujishiro S.H., Tanimura S., Mure S., Kashimoto Y., Watanabe K., Kohno M.;
RT "ERK1/2 phosphorylate GEF-H1 to enhance its guanine nucleotide exchange
RT activity toward RhoA.";
RL Biochem. Biophys. Res. Commun. 368:162-167(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NOD1.
RX PubMed=19043560; DOI=10.1371/journal.ppat.1000228;
RA Fukazawa A., Alonso C., Kurachi K., Gupta S., Lesser C.F., McCormick B.A.,
RA Reinecker H.C.;
RT "GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella
RT effectors.";
RL PLoS Pathog. 4:E1000228-E1000228(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163; SER-645; SER-648;
RP SER-696; SER-886; TYR-894; SER-940; SER-941; SER-956 AND SER-960, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [21]
RP REVIEW ON FUNCTION.
RX PubMed=18394899; DOI=10.1016/j.tcb.2008.02.006;
RA Birkenfeld J., Nalbant P., Yoon S.-H., Bokoch G.M.;
RT "Cellular functions of GEF-H1, a microtubule-regulated Rho-GEF: is altered
RT GEF-H1 activity a crucial determinant of disease pathogenesis?";
RL Trends Cell Biol. 18:210-219(2008).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-172; THR-679; SER-691;
RP SER-696; SER-886; SER-941; THR-945; SER-947; SER-953; SER-956 AND SER-960,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-353, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-956 AND SER-960, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [28]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH NOD2 AND RIPK2, INTERACTION WITH
RP RIPK1; RIPK2 AND RIPK3, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=21887730; DOI=10.1002/ibd.21851;
RA Zhao Y., Alonso C., Ballester I., Song J.H., Chang S.Y., Guleng B.,
RA Arihiro S., Murray P.J., Xavier R., Kobayashi K.S., Reinecker H.C.;
RT "Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1.";
RL Inflamm. Bowel Dis. 18:603-612(2012).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-109; SER-122; SER-129;
RP SER-133; SER-137; SER-151; SER-163; SER-172; SER-174; SER-177; SER-645;
RP SER-711; SER-886; SER-932; SER-956 AND SER-960, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-679 AND SER-956, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [32]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [33]
RP FUNCTION, AND INVOLVEMENT IN NEDMHM.
RX PubMed=28453519; DOI=10.1371/journal.pgen.1006746;
RA Ravindran E., Hu H., Yuzwa S.A., Hernandez-Miranda L.R., Kraemer N.,
RA Ninnemann O., Musante L., Boltshauser E., Schindler D., Huebner A.,
RA Reinecker H.C., Ropers H.H., Birchmeier C., Miller F.D., Wienker T.F.,
RA Huebner C., Kaindl A.M.;
RT "Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-
RT hindbrain malformation.";
RL PLoS Genet. 13:E1006746-E1006746(2017).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 439-582, AND DOMAIN PH.
RX PubMed=26820534; DOI=10.1016/j.bbrc.2016.01.150;
RA Jiang Y., Jiang H., Zhou S., Meng B., Liu Z.J., Ouyang S.;
RT "Crystal structure of hGEF-H1 PH domain provides insight into incapability
RT in phosphoinositide binding.";
RL Biochem. Biophys. Res. Commun. 471:621-627(2016).
CC -!- FUNCTION: Activates Rho-GTPases by promoting the exchange of GDP for
CC GTP. May be involved in epithelial barrier permeability, cell motility
CC and polarization, dendritic spine morphology, antigen presentation,
CC leukemic cell differentiation, cell cycle regulation, innate immune
CC response, and cancer. Binds Rac-GTPases, but does not seem to promote
CC nucleotide exchange activity toward Rac-GTPases, which was uniquely
CC reported in PubMed:9857026. May stimulate instead the cortical activity
CC of Rac. Inactive toward CDC42, TC10, or Ras-GTPases. Forms an
CC intracellular sensing system along with NOD1 for the detection of
CC microbial effectors during cell invasion by pathogens. Required for
CC RHOA and RIP2 dependent NF-kappaB signaling pathways activation upon
CC S.flexneri cell invasion. Involved not only in sensing peptidoglycan
CC (PGN)-derived muropeptides through NOD1 that is independent of its GEF
CC activity, but also in the activation of NF-kappaB by Shigella effector
CC proteins (IpgB2 and OspB) which requires its GEF activity and the
CC activation of RhoA. Involved in innate immune signaling transduction
CC pathway promoting cytokine IL6/interleukin-6 and TNF-alpha secretion in
CC macrophage upon stimulation by bacterial peptidoglycans; acts as a
CC signaling intermediate between NOD2 receptor and RIPK2 kinase.
CC Contributes to the tyrosine phosphorylation of RIPK2 through Src
CC tyrosine kinase leading to NF-kappaB activation by NOD2. Overexpression
CC activates Rho-, but not Rac-GTPases, and increases paracellular
CC permeability (By similarity). Involved in neuronal progenitor cell
CC division and differentiation (PubMed:28453519). Involved in the
CC migration of precerebellar neurons (By similarity).
CC {ECO:0000250|UniProtKB:Q60875, ECO:0000250|UniProtKB:Q865S3,
CC ECO:0000269|PubMed:19043560, ECO:0000269|PubMed:21887730,
CC ECO:0000269|PubMed:28453519, ECO:0000269|PubMed:9857026}.
CC -!- SUBUNIT: Found in a complex composed at least of ARHGEF2, NOD2 and
CC RIPK2. Interacts with RIPK2; the interaction mediates tyrosine
CC phosphorylation of RIPK2 by Src kinase CSK. Interacts with RIPK1 and
CC RIPK3. Interacts with YWHAZ/14-3-3 zeta; when phosphorylated at Ser-
CC 886. Interacts with the kinases PAK4, AURKA and MAPK1. Interacts with
CC RHOA and RAC1. Interacts with NOD1. Interacts (via the N-terminal zinc
CC finger) with CAPN6 (via domain II). Interacts with DYNLT1 (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q865S3}.
CC -!- INTERACTION:
CC Q92974; O43524: FOXO3; NbExp=2; IntAct=EBI-302405, EBI-1644164;
CC Q92974; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-302405, EBI-10271199;
CC Q92974; P61586: RHOA; NbExp=3; IntAct=EBI-302405, EBI-446668;
CC Q92974; Q8N5L8: RPP25L; NbExp=7; IntAct=EBI-302405, EBI-10189722;
CC Q92974; P63104: YWHAZ; NbExp=3; IntAct=EBI-302405, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:11912491, ECO:0000269|PubMed:21887730,
CC ECO:0000269|PubMed:9857026}. Cytoplasm {ECO:0000269|PubMed:15827085,
CC ECO:0000269|PubMed:21887730}. Cell junction, tight junction
CC {ECO:0000269|PubMed:19043560}. Golgi apparatus
CC {ECO:0000269|PubMed:15827085}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:17488622}. Cell projection, ruffle membrane
CC {ECO:0000269|PubMed:19043560}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:21887730}. Note=Localizes to the tips of cortical
CC microtubules of the mitotic spindle during cell division, and is
CC further released upon microtubule depolymerization (PubMed:15827085).
CC Recruited into membrane ruffles induced by S.flexneri at tight
CC junctions of polarized epithelial cells (PubMed:19043560). Colocalized
CC with NOD2 and RIPK2 in vesicles and with the cytoskeleton
CC (PubMed:21887730). {ECO:0000269|PubMed:15827085,
CC ECO:0000269|PubMed:19043560, ECO:0000269|PubMed:21887730}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q92974-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92974-2; Sequence=VSP_039458;
CC Name=3;
CC IsoId=Q92974-3; Sequence=VSP_039457, VSP_039458;
CC -!- INDUCTION: Up-regulated by bacterial peptidoglycans stimulation, such
CC as muramyl dipeptide and in biopsies from inflamed mucosal areas of
CC Crohn's disease patients. {ECO:0000269|PubMed:21887730}.
CC -!- DOMAIN: The DH (DBL-homology) domain interacts with and promotes
CC loading of GTP on RhoA. Promotes tyrosine phosphorylation of RIPK2.
CC -!- DOMAIN: The PH domain has no affinity for phosphoinositides suggesting
CC that it does not interact directly with membranes.
CC {ECO:0000269|PubMed:26820534}.
CC -!- DOMAIN: The phorbol-ester/DAG-type zinc-finger and the C-terminal
CC coiled-coil domains (606-986) are both important for association with
CC microtubules. {ECO:0000269|PubMed:11912491,
CC ECO:0000269|PubMed:9857026}.
CC -!- PTM: Phosphorylation of Ser-886 by PAK1 induces binding to protein
CC YWHAZ, promoting its relocation to microtubules and the inhibition of
CC its activity. Phosphorylated by AURKA and CDK1 during mitosis, which
CC negatively regulates its activity. Phosphorylation by MAPK1 or MAPK3
CC increases nucleotide exchange activity. Phosphorylation by PAK4
CC releases GEF-H1 from the microtubules. Phosphorylated on serine,
CC threonine and tyrosine residues in a RIPK2-dependent manner.
CC {ECO:0000269|PubMed:14970201, ECO:0000269|PubMed:15827085,
CC ECO:0000269|PubMed:17488622, ECO:0000269|PubMed:18211802}.
CC -!- DISEASE: Neurodevelopmental disorder with midbrain and hindbrain
CC malformations (NEDMHM) [MIM:617523]: An autosomal recessive
CC neurodevelopmental disorder characterized by intellectual disability,
CC speech delay, mild microcephaly, midbrain-hindbrain malformations, and
CC variable dysmorphic features. {ECO:0000269|PubMed:28453519}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC97383.1; Type=Miscellaneous discrepancy; Note=Sequence differs at a large extent from the sequence shown in the paper.; Evidence={ECO:0000305};
CC Sequence=AAH20567.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA31626.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA33634.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ARHGEF2ID43150ch1q22.html";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=ARHGEF2 entry;
CC URL="https://en.wikipedia.org/wiki/ARHGEF2";
CC ---------------------------------------------------------------------------
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DR EMBL; U72206; AAC97383.1; ALT_SEQ; mRNA.
DR EMBL; AF486838; AAL96658.1; -; mRNA.
DR EMBL; AB014551; BAA31626.3; ALT_INIT; mRNA.
DR EMBL; AL512715; CAC21656.1; -; mRNA.
DR EMBL; AL355388; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53013.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53015.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53014.1; -; Genomic_DNA.
DR EMBL; BC020567; AAH20567.1; ALT_INIT; mRNA.
DR EMBL; BT007407; AAP36075.1; -; mRNA.
DR EMBL; X15610; CAA33634.1; ALT_FRAME; mRNA.
DR CCDS; CCDS1125.1; -. [Q92974-3]
DR CCDS; CCDS53375.1; -. [Q92974-2]
DR CCDS; CCDS53376.1; -. [Q92974-1]
DR PIR; S28660; S28660.
DR RefSeq; NP_001155855.1; NM_001162383.1. [Q92974-1]
DR RefSeq; NP_001155856.1; NM_001162384.1. [Q92974-2]
DR RefSeq; NP_004714.2; NM_004723.3. [Q92974-3]
DR PDB; 5EFX; X-ray; 2.45 A; A=439-582.
DR PDBsum; 5EFX; -.
DR AlphaFoldDB; Q92974; -.
DR SMR; Q92974; -.
DR BioGRID; 114618; 187.
DR CORUM; Q92974; -.
DR ELM; Q92974; -.
DR IntAct; Q92974; 60.
DR MINT; Q92974; -.
DR STRING; 9606.ENSP00000354837; -.
DR GlyGen; Q92974; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q92974; -.
DR MetOSite; Q92974; -.
DR PhosphoSitePlus; Q92974; -.
DR BioMuta; ARHGEF2; -.
DR DMDM; 205830906; -.
DR EPD; Q92974; -.
DR jPOST; Q92974; -.
DR MassIVE; Q92974; -.
DR MaxQB; Q92974; -.
DR PaxDb; Q92974; -.
DR PeptideAtlas; Q92974; -.
DR PRIDE; Q92974; -.
DR ProteomicsDB; 75638; -. [Q92974-1]
DR ProteomicsDB; 75639; -. [Q92974-2]
DR ProteomicsDB; 75640; -. [Q92974-3]
DR TopDownProteomics; Q92974-2; -. [Q92974-2]
DR Antibodypedia; 20425; 452 antibodies from 33 providers.
DR DNASU; 9181; -.
DR Ensembl; ENST00000313667.8; ENSP00000314787.4; ENSG00000116584.21. [Q92974-2]
DR Ensembl; ENST00000313695.11; ENSP00000315325.7; ENSG00000116584.21. [Q92974-3]
DR Ensembl; ENST00000361247.9; ENSP00000354837.4; ENSG00000116584.21. [Q92974-1]
DR GeneID; 9181; -.
DR KEGG; hsa:9181; -.
DR MANE-Select; ENST00000361247.9; ENSP00000354837.4; NM_001162383.2; NP_001155855.1.
DR UCSC; uc001fmr.3; human. [Q92974-1]
DR CTD; 9181; -.
DR DisGeNET; 9181; -.
DR GeneCards; ARHGEF2; -.
DR HGNC; HGNC:682; ARHGEF2.
DR HPA; ENSG00000116584; Low tissue specificity.
DR MalaCards; ARHGEF2; -.
DR MIM; 607560; gene.
DR MIM; 617523; phenotype.
DR neXtProt; NX_Q92974; -.
DR OpenTargets; ENSG00000116584; -.
DR PharmGKB; PA24972; -.
DR VEuPathDB; HostDB:ENSG00000116584; -.
DR eggNOG; KOG3520; Eukaryota.
DR GeneTree; ENSGT00940000158341; -.
DR HOGENOM; CLU_002466_1_1_1; -.
DR InParanoid; Q92974; -.
DR OrthoDB; 69816at2759; -.
DR PhylomeDB; Q92974; -.
DR TreeFam; TF325887; -.
DR PathwayCommons; Q92974; -.
DR Reactome; R-HSA-193648; NRAGE signals death through JNK.
DR Reactome; R-HSA-416482; G alpha (12/13) signalling events.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013026; RHOB GTPase cycle.
DR SignaLink; Q92974; -.
DR SIGNOR; Q92974; -.
DR BioGRID-ORCS; 9181; 24 hits in 1084 CRISPR screens.
DR ChiTaRS; ARHGEF2; human.
DR GeneWiki; ARHGEF2; -.
DR GenomeRNAi; 9181; -.
DR Pharos; Q92974; Tbio.
DR PRO; PR:Q92974; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q92974; protein.
DR Bgee; ENSG00000116584; Expressed in inferior vagus X ganglion and 208 other tissues.
DR ExpressionAtlas; Q92974; baseline and differential.
DR Genevisible; Q92974; HS.
DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IDA:UniProtKB.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IMP:UniProtKB.
DR GO; GO:0055059; P:asymmetric neuroblast division; IDA:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0000902; P:cell morphogenesis; IMP:UniProtKB.
DR GO; GO:0071474; P:cellular hyperosmotic response; ISS:BHF-UCL.
DR GO; GO:0071225; P:cellular response to muramyl dipeptide; IDA:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:BHF-UCL.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006886; P:intracellular protein transport; NAS:UniProtKB.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISS:BHF-UCL.
DR GO; GO:1902219; P:negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress; ISS:BHF-UCL.
DR GO; GO:0007026; P:negative regulation of microtubule depolymerization; IMP:UniProtKB.
DR GO; GO:0060546; P:negative regulation of necroptotic process; ISS:BHF-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:UniProtKB.
DR GO; GO:2001224; P:positive regulation of neuron migration; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; TAS:UniProtKB.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IBA:GO_Central.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR CDD; cd00029; C1; 1.
DR CDD; cd13393; PH_ARHGEF2; 1.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR037806; ARHGEF2_PH.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR041020; PH_16.
DR InterPro; IPR001849; PH_domain.
DR Pfam; PF17838; PH_16; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division;
KW Cell junction; Cell membrane; Cell projection; Coiled coil; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Developmental protein; Differentiation;
KW Golgi apparatus; Guanine-nucleotide releasing factor; Immunity;
KW Innate immunity; Intellectual disability; Membrane; Metal-binding;
KW Microtubule; Mitosis; Neurogenesis; Phosphoprotein; Reference proteome;
KW Tight junction; Zinc; Zinc-finger.
FT CHAIN 1..986
FT /note="Rho guanine nucleotide exchange factor 2"
FT /id="PRO_0000080909"
FT DOMAIN 235..432
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 472..571
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 39..86
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 131..161
FT /note="Interaction with DYNLT1"
FT /evidence="ECO:0000250|UniProtKB:Q865S3"
FT REGION 683..705
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 862..986
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 587..611
FT /evidence="ECO:0000255"
FT COILED 798..867
FT /evidence="ECO:0000255"
FT COMPBIAS 913..949
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 965..986
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 109
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 122
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 129
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 133
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 143
FT /note="Phosphoserine; by PAK4"
FT /evidence="ECO:0000269|PubMed:15827085"
FT MOD_RES 151
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 163
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 174
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 177
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 353
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 645
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 648
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 679
FT /note="Phosphothreonine; by MAPK1 or MAPK3"
FT /evidence="ECO:0000269|PubMed:18211802,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:24275569"
FT MOD_RES 691
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 696
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332"
FT MOD_RES 711
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 782
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60875"
FT MOD_RES 886
FT /note="Phosphoserine; by PAK1 and AURKA"
FT /evidence="ECO:0000269|PubMed:14970201,
FT ECO:0000269|PubMed:17488622, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 894
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 896
FT /note="Phosphoserine; by PAK4"
FT /evidence="ECO:0000269|PubMed:15827085"
FT MOD_RES 932
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 940
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 941
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 945
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 947
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 952
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60875"
FT MOD_RES 953
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 956
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 960
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17488622,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..27
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005,
FT ECO:0000303|PubMed:9734811"
FT /id="VSP_039457"
FT VAR_SEQ 194
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11912491,
FT ECO:0000303|PubMed:17974005, ECO:0000303|PubMed:9734811"
FT /id="VSP_039458"
FT MUTAGEN 53
FT /note="C->R: Abolishes microtubule binding, increased
FT activity in vitro."
FT /evidence="ECO:0000269|PubMed:11912491"
FT MUTAGEN 143
FT /note="S->A: Abolishes phosphorylation by PAK4, self
FT aggregation in the cytoplasm. Increases activity; when
FT associated with A-896."
FT /evidence="ECO:0000269|PubMed:15827085"
FT MUTAGEN 394
FT /note="Y->A: Reduces phosphorylation level, normal
FT microtubule localization and activity."
FT /evidence="ECO:0000269|PubMed:11912491"
FT MUTAGEN 679
FT /note="T->A: Reduces phosphorylation level."
FT /evidence="ECO:0000269|PubMed:18211802"
FT MUTAGEN 886
FT /note="S->A: Normal activity."
FT MUTAGEN 886
FT /note="S->D: Increases activity. Abolishes nucleotide
FT exchange activity; when associated with D-960."
FT MUTAGEN 896
FT /note="S->A: Abolishes phosphorylation by PAK4, self
FT aggregation in the cytoplasm. Increases activity; when
FT associated with A-143."
FT /evidence="ECO:0000269|PubMed:15827085"
FT MUTAGEN 960
FT /note="S->A: Normal activity."
FT MUTAGEN 960
FT /note="S->D: Increases activity. Abolishes nucleotide
FT exchange activity; when associated with D-886."
FT CONFLICT 1..20
FT /note="MSRIESLTRARIDRSRELAS -> IVGAAGHGRALSLCFDNGPLEQVPLALE
FT ETASIGMPRPQGGPLPADPRRTGHLSGTGHQGGYASRLDQDSCHPSAGPLDHSATGMLS
FT KSVPVSGINCLLDRSDTDGNVSQSSAIDLRKRCSQLEGHSGTRVGSSLRQTFSFLSGMT
FT GKA (in Ref. 3; BAA31626)"
FT /evidence="ECO:0000305"
FT CONFLICT 631
FT /note="M -> L (in Ref. 10; CAA33634)"
FT /evidence="ECO:0000305"
FT CONFLICT 868
FT /note="P -> Q (in Ref. 10; CAA33634)"
FT /evidence="ECO:0000305"
FT HELIX 440..447
FT /evidence="ECO:0007829|PDB:5EFX"
FT STRAND 454..457
FT /evidence="ECO:0007829|PDB:5EFX"
FT TURN 458..460
FT /evidence="ECO:0007829|PDB:5EFX"
FT STRAND 461..464
FT /evidence="ECO:0007829|PDB:5EFX"
FT HELIX 465..469
FT /evidence="ECO:0007829|PDB:5EFX"
FT STRAND 473..482
FT /evidence="ECO:0007829|PDB:5EFX"
FT STRAND 488..504
FT /evidence="ECO:0007829|PDB:5EFX"
FT STRAND 509..511
FT /evidence="ECO:0007829|PDB:5EFX"
FT STRAND 519..522
FT /evidence="ECO:0007829|PDB:5EFX"
FT STRAND 527..530
FT /evidence="ECO:0007829|PDB:5EFX"
FT STRAND 537..542
FT /evidence="ECO:0007829|PDB:5EFX"
FT TURN 543..546
FT /evidence="ECO:0007829|PDB:5EFX"
FT STRAND 547..552
FT /evidence="ECO:0007829|PDB:5EFX"
FT HELIX 556..571
FT /evidence="ECO:0007829|PDB:5EFX"
FT TURN 576..578
FT /evidence="ECO:0007829|PDB:5EFX"
SQ SEQUENCE 986 AA; 111543 MW; 8986AF0A1174EA71 CRC64;
MSRIESLTRA RIDRSRELAS KTREKEKMKE AKDARYTNGH LFTTISVSGM TMCYACNKSI
TAKEALICPT CNVTIHNRCK DTLANCTKVK QKQQKAALLK NNTALQSVSL RSKTTIRERP
SSAIYPSDSF RQSLLGSRRG RSSLSLAKSV STTNIAGHFN DESPLGLRRI LSQSTDSLNM
RNRTLSVESL IDEAEVIYSE LMSDFEMDEK DFAADSWSLA VDSSFLQQHK KEVMKQQDVI
YELIQTELHH VRTLKIMTRL FRTGMLEELH LEPGVVQGLF PCVDELSDIH TRFLSQLLER
RRQALCPGST RNFVIHRLGD LLISQFSGPS AEQMCKTYSE FCSRHSKALK LYKELYARDK
RFQQFIRKVT RPAVLKRHGV QECILLVTQR ITKYPLLISR ILQHSHGIEE ERQDLTTALG
LVKELLSNVD EGIYQLEKGA RLQEIYNRMD PRAQTPVPGK GPFGREELLR RKLIHDGCLL
WKTATGRFKD VLVLLMTDVL VFLQEKDQKY IFPTLDKPSV VSLQNLIVRD IANQEKGMFL
ISAAPPEMYE VHTASRDDRS TWIRVIQQSV RTCPSREDFP LIETEDEAYL RRIKMELQQK
DRALVELLRE KVGLFAEMTH FQAEEDGGSG MALPTLPRGL FRSESLESPR GERLLQDAIR
EVEGLKDLLV GPGVELLLTP REPALPLEPD SGGNTSPGVT ANGEARTFNG SIELCRADSD
SSQRDRNGNQ LRSPQEEALQ RLVNLYGLLH GLQAAVAQQD TLMEARFPEG PERREKLCRA
NSRDGEAGRA GAAPVAPEKQ ATELALLQRQ HALLQEELRR CRRLGEERAT EAGSLEARLR
ESEQARALLE REAEEARRQL AALGQTEPLP AEAPWARRPV DPRRRSLPAG DALYLSFNPP
QPSRGTDRLD LPVTTRSVHR NFEDRERQEL GSPEERLQDS SDPDTGSEEE GSSRLSPPHS
PRDFTRMQDI PEETESRDGE AVASES
